We have previously shown that coronary vascular resistance is elevated in the diabetic lamb (Am. J. Physiol. 237:H118, 1979), and that coronary dilator responses to insulin and aminophylline are much reduced. The objective of this study is to examine coronary vasomotor responses to adenosine, a principal regulator of coronary blood flow. Lambs will be rendered diabetic with alloxan (150 micrograms/kg). Using a hemodynamically controlled, open chest preparation, coronary flow will be continously measured and myocardial O2 extraction, and O2 and glucose uptake determined. Changes in coronary flow (and resistance) will be measured in response to intravenous and left atrial infusions of increasing concentrations of adenosine (3-30 micrograms/kg/min). Mechanical performance of the heart will be assessed from measurements of stroke volume, LV dP/dt max and LVEDP. Myocardial O2 metabolism will be calculated. Comparison will be made between controls and lambs diabetic for 2-4 days and 2-4 weeks. The immediate effects of insulin, and the consequences of insulin replacement in the diabetics will be examined. The objective will be to determine if altered coronary reactivity to adenosine can be prevented or reversed. A second goal is to compare inotropic sensitivity to alpha (methoxamine) and beta (isoproterenol) agonists in control and diabetic preparations, and to assess the potential for reversibility by insulin replacement. The same hemodynamically controlled preparations will be employed, and myocardial responsiveness will be determined from dose-response curves.